Relapsed or Refractory CD30-Positive Diffuse Large B-Cell Lymphoma MedDRA version: 19.1 Level: PT Classification code 10012822 Term: Diffuse large B-cell lymphoma refractory System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 19.1 Level: LLT Classification code 10067070 Term: Follicular B-cell non-Hodgkin's lymphoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
Seattle Genetics, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patients with histologically confirmed CD30-positive DLBCL or follicular non-Hodgkin lymphoma (NHL) grade 3b, defined as any detectable CD30 expression on tumor cells based on local or central pathologic assessment. 2. Patients must have relapsed or refractory disease following: a. second-line or greater salvage systemic therapy, or b. frontline cytotoxic systemic therapy, for patients who are ineligible for stem cell transplant (SCT). 3. Age 18 and older. 4. Fluorodeoxyglucose (FDG)-avid disease by positron emission tomography (PET) and measurable disease of at least 1.5 cm by computed tomography (CT), as assessed by the site radiologist. 5. An Eastern Cooperative Oncology Group (ECOG) performance status score of 0–2. 6. The following baseline laboratory data: a. Absolute neutrophil count (ANC) =1000/µL (unless documented bone marrow involvement) b. Platelet count =75,000/µL (unless documented bone marrow involvement) c. Serum bilirubin =1.5 × upper limit of normal (ULN) or =3 × ULN for patients with Gilbert’s disease d. Estimated creatinine clearance (CrCL) =40 mL/min (calculated using the Cockcroft-Gault formula) e. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =2.5 × ULN. 7. Females of childbearing potential must have a negative serum or urine beta human chorionic gonadotropin (ß-hCG) pregnancy test result within 7 days prior to the first dose of study drug. Females of non-childbearing potential are those who are postmenopausal greater than 1 year or who have had a bilateral tubal ligation or bilateral oophorectomy or hysterectomy. 8. Females of childbearing potential and males who have partners of childbearing potential must agree to use 2 effective contraceptive methods during the study and for 6 months following the last dose of brentuximab vedotin or 12 months following the last dose of rituximab, whichever is later. 9. Patients must be willing and able to provide written informed consent. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 55 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 55
Exclusion criteria
Exclusion criteria: 1. History of another invasive malignancy that has not been in remission for at least 1 year. The following are exempt from the 1-year limit: nonmelanoma skin cancer, curatively treated localized prostate cancer, ductal carcinoma in situ (DCIS), and cervical carcinoma in situ on biopsy or a squamous intraepithelial lesion on PAP smear. 2. History of progressive multifocal leukoencephalopathy (PML). 3. Cerebral/meningeal disease related to the underlying malignancy. Patients with a history of cerebral/meningeal disease related to the underlying malignancy are allowed if prior central nervous system (CNS) disease has been definitively treated. 4. Any active Grade 3 or higher (per the National Cancer Institute [NCI, US] Common Terminology Criteria for Adverse Events [CTCAE] Version 4.03) viral, bacterial, or fungal infection within 2 weeks prior to the first dose of brentuximab vedotin. Routine antimicrobial prophylaxis is permitted. 5. Chemotherapy, radiotherapy, biologics, and/or other antitumor treatment with immunotherapy that is not completed 4 weeks prior to first dose of study drug. Concomitant use of other systemic antineoplastic agents (including bleomycin) while on study is excluded. 6. Females who are pregnant or breastfeeding. 7. Known hypersensitivity to any study drug or excipient contained in the drug formulation of any of the study drugs. 8. Known to be positive for hepatitis B by surface antigen expression (HBsAg) and hepatitis B core antibody (HBcAb). Known to have active hepatitis C infection (positive by polymerase chain reaction) or on antiviral therapy for hepatitis C within the last 6 months. 9. Known to be positive for human immunodeficiency virus (HIV). 10. Patients with previous allogeneic SCT. 11. Previous treatment with brentuximab vedotin or bendamustine. 12. Intolerable toxicity to prior rituximab therapy (per Investigator discretion). 13. Current therapy with other investigational agents. 14. Grade 3 or higher pulmonary disease unrelated to underlying malignancy. 15. Documented history of a cerebral vascular event (stroke or transient ischemic attack), unstable angina, myocardial infarction, or cardiac symptoms consistent with New York Heart Association (NYHA) Class III-IV within 6 months prior to the first dose of brentuximab vedotin. 16. Congestive heart failure, Class III or IV, by the NYHA criteria. 17. Grade 2 or higher (per NCI CTCAE, Version 4.03) peripheral sensory or motor neuropathy at baseline. 18. Major surgery less than 30 days prior to first dose of study drug. Major surgery is any invasive operative procedure in which a more extensive resection is performed, eg, a body cavity is entered, organs are removed, or normal anatomy is altered. 19. Live vaccines (in particular yellow fever vaccination) within 1 month prior to the first dose of study drug. 20. Current severe immunodeficiency, or history of recurring or chronic infections, or underlying conditions which may further predispose patients to serious infection.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the objective response rate (ORR) among subjects with relapsed or refractory CD30-positive DLBCL or follicular non-Hodgkin lymphoma (NHL) grade 3b receiving rituximab and bendamustine plus brentuximab vedotin (treatment arm) with that among subjects receiving rituximab and bendamustine alone (control arm) ;Secondary Objective: -To compare progression-free survival (PFS) among subjects with relapsed or refractory CD30-positive DLBCL or follicular NHL grade 3b receiving rituximab and bendamustine plus brentuximab vedotin (treatment arm) with that among subjects receiving rituximab and bendamustine alone (control arm) -To compare the complete remission (CR) rate between the 2 arms of the study -To compare duration of response (DOR) between the 2 arms of the study -To compare overall survival (OS) between the 2 arms of the study -To evaluate the safety and tolerability of the 2 arms of the study ;Primary end point(s): The primary efficacy endpoint of this study is objective response rate (ORR) as assessed by the 2014 Lugano Classification. ;Timepoint(s) of evaluation of this end point: Imaging (CT and PET or CT/PET; PET no longer required after documented postbaseline FDG-negative PET) at the end of Cycles 2 and 6; 6, 12, and 24 months after the start of combination treatment (Cycle 1, Day 1); and annually thereafter until disease progression or study closure). | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary efficacy endpoints are the following: - Progression-free survival - Complete response rate -Best clinical response -Duration of response -Overall survival -Type, incidence, severity, seriousness, and relatedness of AEs - Type, incidence, and severity of laboratory abnormalities - Incidence and severity of infusion-related and hypersensitivity reactions.;Timepoint(s) of evaluation of this end point: Please refer to Table 2 of the study protocol (Study Schedule), page 43 of 126 | — |
Countries
Czech Republic, France, Italy, Poland, Spain, United Kingdom, United States
Contacts
Public ContactNikki Bindra
PRA Health Sciences
Outcome results
None listed